Clinical implications of assessment of apixaban levels in elderly atrial fibrillation patients: J-ELD AF registry sub-cohort analysis

Suzuki, Shinya; Yamashita, Takeshi; Akao, Masaharu; Okumura, Ken; investigators, J-Eld Af

doi:10.1007/s00228-020-02896-y

Cited by 13 publications

(5 citation statements)

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“…As noted, 84.4 % of our extremely low body weight group received a reduced dose of apixaban. Given that there was an obvious difference in the occurrence of bleeding requiring hospitalization between subjects with high and low blood apixaban levels in patients receiving a reduced apixaban dose in the subanalysis of the J-ELD AF Registry [28], the existence of a further high-risk subpopulation in the extremely low body weight group should have been presumed, which unfortunately could not be determined from our current data. There was no evidence that should take into account the effect of competing risk of total death, because there was no obvious difference in HR of the extremely low body weight group between the Cox model and the Fine-Gray model (Supplement Table S1).…”

Section: Discussionmentioning

confidence: 75%

“…[28] Nevertheless, there was no signi cant difference in the occurrence of stroke or systemic embolism among the body weight groups, which suggests that apixaban level does not affect stroke and systemic embolism irrespective of apixaban dose. [28] There was no evidence that should take into account the effect of competing risk of total death, because there was no obvious difference in HR of the extremely low body weight group between the Cox model and the Fine-Gray model (Supplement Table S1). When comparing the risk of low body weight or extremely low body weight on stroke or systemic embolism between standard and reduced doses, there was no signi cant interaction between body weight and apixaban dose, which may partially con rm the validity of the criteria for reduction of apixaban dose in view of the effect of low body weight (Supplement Figure 1).…”

Section: Discussionmentioning

confidence: 84%

“…Notably, 84.4 % of our extremely low body weight group received a reduced apixaban dose, which was associated with a lower blood level of apixaban compared to the standard dose in a previous subanalysis of the J-ELD AF Registry. [28] Nevertheless, there was no signi cant difference in the occurrence of stroke or systemic embolism among the body weight groups, which suggests that apixaban level does not affect stroke and systemic embolism irrespective of apixaban dose. [28] There was no evidence that should take into account the effect of competing risk of total death, because there was no obvious difference in HR of the extremely low body weight group between the Cox model and the Fine-Gray model (Supplement Table S1).…”

Section: Discussionmentioning

confidence: 84%

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Effectiveness and Safety of Apixaban in Japanese Elderly Atrial Fibrillation Patients With Extremely Low Body Weight

Kadosaka¹,

Nagai²,

Suzuki³

et al. 2021

Preprint

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Purpose Although direct oral anticoagulants are effective and safe in preventing stroke in atrial fibrillation (AF) patients with low body weight, data remain limited in AF patients with extremely low body weight (< 50 kg). We aimed to investigate the effectiveness and safety of apixaban in this category of patients. Methods The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban. The entire cohort (3,025 patients from 110 institutions) was divided into three body weight subgroups: >60 kg (n = 1,019, 33.7 %), 50–60 kg (n = 1,126, 37.2 %), and < 50 kg (n = 880, 29.1%). Results The event incidence rates (/100 person-years) were 1.69, 1.82 and 1.23 for stroke or systemic embolism (P = 0.60); 1.37, 1.73 and 2.73 for bleeding requiring hospitalization (P = 0.154); 2.02, 2.67 and 4.92 for total death (P = 0.003); and 0.73, 0.95 and 1.23 for cardiovascular death (P = 0.57), respectively. After adjusting for confounders by Cox regression analysis, body weight < 50 kg was an independent risk for total death but not for stroke or systemic embolism, bleeding requiring hospitalization or cardiovascular death. Conclusions The incidence of events in each body weight group was comparable for stroke or systemic embolism, bleeding requiring hospitalization, and cardiovascular death, and significantly higher for total death in the body weight < 50 kg group in Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 84%

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Effectiveness and Safety of Apixaban in Japanese Elderly Atrial Fibrillation Patients With Extremely Low Body Weight

Kadosaka¹,

Nagai²,

Suzuki³

et al. 2021

Preprint

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“…However, the real-world pilot prospective study reported significantly higher C trough and C peak values in the bleeding group compared with the non-bleeding group [ 36 ], which is similar to our study. Concomitant with CYP3A4 and P-gp inhibitors, older age was a factor causing high apixaban plasma levels in the bleeding group [ 37 , 38 ]. Many reports demonstrated drug interactions and the effect of age on the apixaban levels [ 7 , 26 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Do Apixaban Plasma Levels Relate to Bleeding? The Clinical Outcomes and Predictive Factors for Bleeding in Patients with Non-Valvular Atrial Fibrillation

et al. 2022

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Apixaban can significantly prevent stroke events in patients with non-valvular atrial fibrillation (NVAF), as can be observed from the large, randomized, controlled trial conducted in the present study. However, the real-world evidence of bleeding events related to the apixaban plasma levels in Asian populations is limited. This study aimed to investigate the apixaban plasma levels and clinical outcomes among NVAF patients receiving apixaban, including determining the risk factors associated with bleeding during routine care. Seventy-one patients were included in the study. The median values were 112.79 (5–95th percentiles: 68.69–207.8) μg/L and 185.62 (5–95th percentiles: 124.06–384.34) μg/L for the apixaban trough (Ctrough) and apixaban peak plasma levels (Cpeak), respectively. Stroke and bleeding were found in 8 (11.27%) and 14 patients (19.72%), respectively. There was no statistical significance for Ctrough and Cpeak in the stroke and non-stroke groups, respectively. The median of Ctrough (139.15 μg/L) in patients with bleeding was higher than that in the non-bleeding group (108.14 μg/L), but there was no statistical significance. However, multivariate analyses showed that bleeding history (odds ratio (OR): 17.62; 95% confidence interval (CI): 3.54–176.64; and p-value = 0.002) and Ctrough (OR: 1.01; 95%: CI 1.00–1.03; and p-value = 0.038) were related to bleeding events. Almost all of the patients presented apixaban plasma levels within the expected range. Interestingly, bleeding events were associated with the troughs of the apixaban plasma levels and bleeding history.

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“…Несмотря на более высокую актуальность проблемы частого использования необоснованно сниженной дозы апиксабана, нельзя не отметить необходимость снижения доз апиксабана при наличии соответствующих критериев, которые были приведены ранее. В частности, это мы наблюдаем в результатах анализа данных об участниках многоцентрового проспективного обсервационного исследования J-ELD AF Registry [30], в который были включены 3 015 жителей Японии 75 лет и старше, которые принимали рекомендуемую дозу апиксабана. У 943 пациентов измеряли минимальную активность антифактора Ха в крови.…”

Section: обоснованное снижение дозы апиксабана как необходимое условие обеспечения безопасности терапииunclassified

Systematic errors in the choice of dose level of direct oral anticoagulants: urgency of an issue and approaches to its solution

et al. 2021

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The article presents updated information on the frequency of use of non-recommended low dosing of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban). It gives substantiation of the urgency of the issue of providing the maximum efficiency of the use of anticoagulants in clinical practice, taking into account the high prevalence of atrial fibrillation and the pharmacological characteristics of the most commonly used drugs. The effects of such an unreasonable reduction in anticoagulant doses in elderly and senile patients are discussed. The results of recent observational studies that assessed the relationship between the use of direct oral anticoagulants and the risk of adverse clinical outcomes are presented. The data on the relationship between the use of unreasonably low dosing of anticoagulants in patients with atrial fibrillation, which were recently obtained during the implementation of the GARFIELD-AF registry, are discussed. The data on a rather high variability of concentrations of direct oral anticoagulants are presented. The frequency of using apixaban in an unreasonably reduced dose, as well as the effects of using non-recommended doses of apixaban hold a specific place in the article. The unreasonableness of attempts to further reduce the risk of bleeding due to unreasonable reduction of apixaban dosing is emphasized, taking into account the stable data on the high safety of recommended dosing of apixaban, as well as the possible decrease in the effect if the dose reduction is not recommended. The data on the criteria for dose reduction, which are adopted in different countries, are presented. The proposed terms to designate different doses of direct oral anticoagulants, depending on their study in the course of large, randomized trials are discussed.

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Clinical implications of assessment of apixaban levels in elderly atrial fibrillation patients: J-ELD AF registry sub-cohort analysis

Cited by 13 publications

References 24 publications

Effectiveness and Safety of Apixaban in Japanese Elderly Atrial Fibrillation Patients With Extremely Low Body Weight

Effectiveness and Safety of Apixaban in Japanese Elderly Atrial Fibrillation Patients With Extremely Low Body Weight

Do Apixaban Plasma Levels Relate to Bleeding? The Clinical Outcomes and Predictive Factors for Bleeding in Patients with Non-Valvular Atrial Fibrillation

Systematic errors in the choice of dose level of direct oral anticoagulants: urgency of an issue and approaches to its solution

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